A rare familial cancer syndrome involving childhood sarcoma, breast cancer, brain tumors, and an array of other tumors has been described (1.2). Survivors of the first tumor seen to be at significant risk of additional tumors of similar types, this risk enhanced by radiation. We wish to determine the frequency of this familial syndrome among 500 three-year survivors of childhood sarcomas, to determine the most likely model of inheritance, and to characterize the clinical phenotype with respect to age, sex, and site specific cancer risks. An estimated 500 three-year survivors of childhood sarcomas will be identified, located, and their families interviewed to determine their current health status, occurrence of new tumors, and familial and reproductive histories. All reported cancers and deaths in a defined set of relatives will be verified. The relative risks of cancer, of all types and of specific types, will be determined by specific relative groups, and proband characteristics. Segregation analysis will be used to explore familial aggregation of cancer to test for etiologic heterogeneity, and to derive parameters of the model(s) which characterize the observed distribution of cancer in these families. Survival analysis will be used to determine whether demographic variables, treatment variables (x-radiation, chemotherapy) and /or genetic - familial variables are significant in a model to predict individuals at high risk of developing a second tumor. This cancer-predisposing syndrome is unique because of its apparent broad tissue specificity and possible enhancement of cancer susceptibility to environmental mutagens. Eventually these findings may be used to identify specific kindreds of genetic linkage study and to develop optimal clinical management.